Nitrofurantoin

Nitrofurantoin (furadantin, macrobid, others) is a synthetic nitrofuran that is used to prevent and treat urinary tract infections. Bacteria reduce nitrofurantoin to toxic products that apparently mediate cell damage. The antibacterial activity is higher in acidic urine.

Pharmacology and Toxicity

Nitrofurantoin is absorbed rapidly and completely from the GI tract. Antibacterial concentrations are not achieved in plasma at recommended doses because the drug is eliminated rapidly. The plasma t/2 is <1 hour; ~40% is excreted unchanged in the urine. The urine should not be alka-linized because this reduces antimicrobial activity. Nitrofurantoin colors the urine brown.

The most common side effects are anorexia, nausea and vomiting, and diarrhea. Hypersensi-tivity reactions occur occasionally, including fever, leukopenia, granulocytopenia, hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency, cholestatic jaundice, and hepatitis. Acute pneumonitis may occur acutely; the symptoms usually resolve quickly after drug discontinuation. Subacute reactions also may occur, including interstitial pulmonary fibrosis. Elderly patients are especially susceptible to the pulmonary toxicity. Severe polyneuropathies affecting both sensory and motor nerves also have been reported, most often in patients with impaired renal function and in persons on long-term treatment.

The oral dosage of nitrofurantoin for adults is 50—100 mg four times a day with meals and at bedtime. A single 50- to 100-mg dose at bedtime may be sufficient to prevent recurrences. A course of therapy should not exceed 14 days. Pregnant women, individuals with impaired renal function (creatinine clearance <40 mL/min), and children <1 month of age should not receive nitrofurantoin.

Nitrofurantoin is approved only for the treatment of urinary tract infections caused by microorganisms known to be susceptible to the drug. Nitrofurantoin is not recommended for treatment of pyelonephritis or prostatitis but is effective for prophylaxis of recurrent urinary tract infections.

For a complete Bibliographical listing see Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th ed., or Goodman & Gilman Online at www.accessmedicine.com.

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